Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury

Drug Delivery

Jingqiu Cheng¹  Yijie Zhou¹  Younan Chen¹  Shuyun Liu¹  Jingping Liu¹  Yanrong Lu¹  Meng Zhao¹  Lan Li¹ 

[1] Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Chin;

关键词: Acute kidney injury;    mitochondria;    Mito-TEMPO;    self-assembling peptide;    control release;   

DOI  :  10.1080/10717544.2018.1440445

来源: publisher

【 摘 要 】

Persistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a robust platform for drug delivery. This study aims to develop an SAP-based carrier to slow release MT for enhancing its long-term therapeutic potency on AKI. The KLD with aspartic acid (KLDD) was designed. The microstructure and in vitro release of MT was assayed. The protective role of MT-loaded SAP (SAP-MT) hydrogel on renal mitochondrial injury, tubular apoptosis, and inflammation was evaluated in mice at five days after ischemia-reperfusion injury (IRI). Our results showed that KLDD could self-assemble into cross-linked nanofiber hydrogel and it had lower release rate than free MT and KLD hydrogel. Compared to IRI and free MT mice, SAP-MT mice exerted reduced renal mitochondria-produced ROS (mtROS) and improved mitochondrial biogenesis and architecture. Consequently, SAP-MT mice showed less renal tubular cell apoptosis, kidney injury marker kidney injury molecule-1 (Kim-1) expression, lower level of pro-inflammatory factors expression, and macrophages infiltration than those of IRI and free MT mice. This study suggested that SAP-MT ameliorated IRI due to its extended mitochondrial protection role than free MT and thus improved the long-term outcomes of AKI.

【 授权许可】

CC BY